Regulation of gene transcription is the primary process by which a cell controls the appropriate expression of the multitude of genes necessary for growth and differentiation. The selective expression of genes at appropriate times is highly specialized in cells of multicellular organisms and permits the cells to perform "housekeeping" functions and respond to changes in their environment. These changes involve extracellular signals from a variety of sources such as hormones, neurotransmitters, and growth and differentiation factors.
Gene transcription is controlled by proteins termed regulators of gene transcription (RGT). RGTs act by binding to a short segment of DNA (transcription control element, TCE) located near the site of transcription initiation. Binding of an RGT to the target TCE activates transcription of the gene. RGTs contain a variety of structural motifs that, alone or in combination with one another, permit them to recognize and bind to the wide variety of TCEs.
One group of RGTs, the TFIIIA subclass of zinc-finger proteins, is characterized by an amino acid motif (a cysteine followed by two to four amino acids, a cysteine, twelve amino acids, a histidine, three to four amino acids, and a histidine) that interacts with zinc ions. The carboxyl terminus of the TFIIIA proteins has three of these "zinc finger" motifs and specifically binds to DNA fragments containing a CACCC pattern. The amino-terminal portion of the TFIIIA proteins is proline and serine-rich and can function as a transcriptional activator.
TFIIIA proteins are often important for the proper differentiation of tissues in which they are expressed. For example, the erythroid Kruppel-like factor (EKLF) is a TFIIIA subclass zinc-finger protein that is expressed in erythroid cells and regulates the B-globin gene. Loss of functional EKLF in mice results in lethal anemia since B-globin is not synthesized (Perkins A. C. et al (1995) Nature 375: 318-322). Another member of this class of proteins, WT-1, is expressed during embryogenesis in the kidney and genital tissues (Pritchard-Jones K. et al. (1990) Nature 346: 194-197). In mice loss of functional WT-1 protein results in failure of the kidney and gonads to form (Kreidberg J. A. et al. (1993) Cell 74:679-691). Mouse BKLF has also been characterized as a erythroid Kruppel-like transcription factor (GI 1244515).
Discovery of proteins related to mouse BKLF and the polynucleotides encoding them satisfies a need in the art by providing new compositions useful in diagnosis, prevention, and treatment of cancer, arthritis, and developmental disorders.